Reproductive toxicology. Nitrofurazone.

Nitrofurazone (NF), part of a large and clinically useful class of antibacterial nitroaro-matic agents, was tested for its effects on reproduction and fertility in Swiss CD-1 mice using the RACB protocol. Data from a 2-week dose-range-finding study (Task 1) were used to set exposure concentrations for the Task 2 continuous cohabitation study at 100, 375, and 750 ppm in feed. Measures of food consumption and body weights produced estimated daily dosages of 12, 47, and 100 mg/kg/day. One middle dose mouse died during Task 2, as did 2 high dose mice. These deaths were judged by the study pathologist as not related to NF consumption. Body weights and food consumption were not reduced during Task 2. The slight increase in measured food consumption was observed to be the result of excess manipulation of the food by the mice, resulting in excess spillage. NF had significant reproductive effects. Even at the first litter in the high dose group, fewer litters were delivered (3/18) compared to the controls (39/40). No high dose pair delivered a third, fourth, or fifth litter. In the middle dose group, the proportion of pairs delivering a litter was reduced starting with the second litter and progressively decreasing. Accordingly, the average number of litters per pair was reduced by 23 and 77% in the 375 and 750 ppm groups, respectively. Live pups per litter were reduced by 40% in the medium dose group. The reduction in numbers of pups per litter at the high dose was overwhelmed by the total absence of litters. Adjusted live pup weight dropped by 10% for the high dose group. Cumulative days to litter was not affected. The last litter from all groups (control , low, and middle dose) was reared by the dam until weaning at postnatal day 21. Postnatal survival was reduced by approximately 30% at the middle dose, and those pups weighed approximately 20 to 40% less than the controls. The low dose pups were not different from controls. After the last litter was reared and weaned, a crossover mating trial was performed to determine the affected sex, using control and high dose mice. For pairs containing treated males, 16% fewer (compared to controls) mated, and none of the mated females produced any young. For pairs with treated females, the number of live pups per litter was half the control value of 10 pups per litter. Pup weight adjusted for …